Phase 1, First-in-Human, Dose Escalation Study of JNJ-79635322, a Trispecific Antibody, in Participants with Relapsed or Refractory Multiple Myeloma

1) >=18 years of age (or the legal age of consent in the jurisdiction in
which the study is taking place) at the time of informed consent.
2) Have documented initial diagnosis of multiple myeloma according to
IMWG diagnostic criteria (Appendix 10.9)
3) Have relapsed or refractory disease and have been treated with a
proteasome inhibitor, IMiD agent, and an anti-CD38-based therapy for
the treatment of MM
4) Have measurable disease at screening as defined by at least 1 of the
following:
a. Serum M-protein level >=0.5 g/dL; or
b. Urine M-protein level >=200 mg/24 hours; or
c. Light chain multiple myeloma: Serum Ig FLC >=10 mg/dL and abnormal
serum Ig kappa lambda FLC ratio.
d. For participants without measurable disease in the serum, urine, or
involved FLC, presence of plasmacytomas (>=2 cm).
5) Clinical laboratory values meeting the following criteria prior to
treatment (see protocol pages 32 - 33)
6) Must have an ECOG status of 0 or 1
7) A female participant of childbearing potential must have a negative
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highly sensitive serum ß hCG test at screening and a negative urine or
serum pregnancy test within 72 hours before the start of study
treatment administration and must agree to further serum or urine
pregnancy tests during the study
8) A female participant must be
a. Not of childbearing potential, or
b. Of childbearing potential and practicing at least 1 highly effective
method of contraception and agrees to remain on a highly effective
method while receiving study drug and until 6 months after last dose.
The investigator should evaluate the potential for contraceptive method
failure (eg, noncompliance, recently initiated) in relationship to the first
dose of study drug.
Note: If a female participant becomes of childbearing potential after the
start of the study, the female participant must comply with (b.).
9) A female participant must agree not to donate eggs (ova, oocytes) or
freeze for future use for the purposes of assisted reproduction during
the study and for a period of 6 months after last dose of study
treatment. Female participants should consider preservation of eggs
prior to study treatment as anticancer treatments may impair fertility
10) A male participant must wear a condom when engaging in any
activity that allows for passage of ejaculate to another person during the
study and for 3 months after receiving the last dose of study treatment.
If partner is a female person of childbearing potential, the male
participant must use condom (with or without spermicide) and the
partner must also be practicing a highly effective method of
contraception (see Appendix 10.5). A male participant who is
vasectomized must still use a condom (with or without spermicide), but
the partner is not required to use contraception.
11) A male participant must agree not to donate sperm for the purpose
of reproduction during the study and for a minimum of 3 months after
receiving the last dose of study drug. Male participants should consider
preservation of sperm prior to study treatment as anticancer treatments
may impair fertility
Informed Consent
12) Must sign an ICF (or their legally acceptable representative must
sign) indicating that the participant understands the purpose of, and
procedures required for, the study and is willing to participate in the
study
13) Be willing and able to adhere to the lifestyle restrictions specified in
this protocol

1) Central nervous system involvement or clinical signs of meningeal
involvement of multiple myeloma. If either is suspected, whole brain
MRI and lumbar cytology are required during screening
2) Active plasma cell leukemia, Waldenström's macroglobulinemia,
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, Mprotein,
and skin changes), or primary light chain amyloidosis.
3) Pulmonary compromise requiring supplemental oxygen used to
maintain adequate oxygenation
4) Any serious underlying medical conditions, such as:
a. Evidence of active viral, bacterial, or systemic
fungal infection requiring ongoing antiviral, antibacterial, or antifungal
treatment.
b. Active autoimmune disease requiring systemic immunosuppressive
therapy within 6 months before start of study treatment. EXCEPTION:
Participants with vitiligo, type I diabetes, and prior autoimmune
thyroiditis that is currently euthyroid based on clinical symptoms and
laboratory testing are eligible regardless of when these conditions were
diagnosed.
c. Disabling psychiatric conditions, substance abuse (eg, alcohol or drug
abuse), severe dementia, or altered mental status
d. Any other issue that would impair the ability of the participant to
receive or tolerate the planned treatment at the investigational site, to
understand the informed consent, or any condition for which, in the
opinion of the investigator, participation would not be in the best
interest of the participant (eg, compromise the well-being of the
participant) or that could prevent, limit, or confound the protocolspecified
assessments.
5) Have a prior or concurrent second malignancy (other than the disease
under study) which natural history or treatment is likely to interfere
with any study endpoints of safety or the efficacy of the study
treatment(s)
6) History of stroke or seizure within 6 months prior to the first dose of
study treatment
7) History of any of the following cardiac conditions
a. New York Heart Association stage III or IV congestive heart failure.
b. Myocardial infarction, unstable angina, or coronary artery bypass graft
<=6 months prior to enrollment.
c. History of clinically significant ventricular arrhythmia or unexplained
syncope not believed to be vasovagal in nature or due to dehydration.
d. History of severe nonischemic cardiomyopathy.
e. Screening 12-lead triplicate ECG showing an average baseline QTc interval of
>470 msec
8) Known allergies, hypersensitivity, or intolerance to excipients of JNJ-
79635322
Prior/Concomitant Therapy or Clinical Study Experience
9) Prior antitumor therapy as follows, in the specified time frame prior to
the first dose of study treatment:
a. Targeted therapy, epigenetic therapy, mAb treatment, or treatment
with an investigational drug or an invasive investigational medical
device within 21 days or at least 5 half-lives, whichever is less.
b. Gene-modified adoptive cell therapy (eg, CAR modified T cells, natural
killer cells) within 90 days.
c. Prior treatment with CD3-redirecting therapy within 21 days prior to
first dose of study treatment.
Note: Prior exposure to BCMA or GPRC5D targeting agents may be
allowed after discussion with the sponsor.
d. Conventional chemotherapy within 21 days.
e. PI therapy within 14 days.
f. Immunomodulatory agent therapy within 7 days.
g. Radiotherapy within 14 days. However, if palliative focal radiation was
used, the participant is eligible irrespective of the end date of
radiotherapy.
10) Received a cumulative dose of corticosteroids equivalent to >140 mg
of prednisone within the 14-day period before the start of study
treatment administration
11) Nonhematologic toxicity from prior anticancer therapy that has not
resolved to baseline level or to less than or equal to Grade 1 (except
alopecia, tissue post-RT fibrosis [any grade] or peripheral neuropathy<=
3)
12) Stem cell transplantation:
a. Allogeneic stem cell transplant within 6 months before the start of study
treatment administration. Participants who
received an allogeneic transplant must be off all immunosuppressive
medications for >=42 days without signs of graft-versus-host disease.
b. Received an autologous stem cell transplant <=12 weeks before the start of
study treatment administration.
13) Trauma or major surgery (eg, requiring general anesthesia) within 2
weeks, or participant will not have fully recovered from surgery, or
participant has surgery planned during the time he or she is expected to
participate in the study. Participants with planned surgical procedures to
be conducted under local anesthesia may participate.
14) Pregnant, breastfeeding, or planning to become pregnant while
enrolled in this study or within 6 months after the last dose of study
drug
15) Plans to father a child while enrolled in this study or within 3 months
after the last dose of study drug
16) Known history of HIV infection
17)Active hepatitis B and hepatitis C infection
18) Received live attenuated vaccine within 4 weeks before first dose of
treatment
19) Body weight <40kg at screening or at the time of the first
administration of study drug